| Co-Investigator(Kenkyū-buntansha) |
MIYAMAE Takako CU SCHOOL OF MEDICINE PEDIATRICS ASSISTANT, 医学部・附属病院, 助手 (90322354)
MORI Masaaki YCU SCHOOL OF MEDICINE PEDIATRICS ASSOC-PROFESSOR, 医学部・附属病院, 助手 (30254204)
AIHARA Yuko YCU SCHOOL OF MEDICINE PEDIATRICS ASSOC-PROFESSOR, 医学部・附属病院, 助教授 (50211686)
伊部 正明 横浜市立大学, 附属病院, 講師 (00232588)
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| Research Abstract |
From the middle of 1990's, it showed a synchronizing phenomenon of epidemics between influenza and encephalopathy in National Surveillance Records in Japan. Pediatricians engaged in emergency room have recognized that in winter season, when influenza is spreading around, there has been a tendency o see children affected with encephalopathy. In 1998, Morishima and his colleagues started investigation to reveal this synchronization and pathophysiology of influenza-associated encephalopathy.
The following numbers of patients were enrolled with influenza-associated encephalopathy; 202 patients in 1998/99 season 96 patients in 1999/2000 season, and 56 patients in 2000/2001 season. The first and second surveillance demonstrated that 33% of patients in each season were dead, and 11 to 13% had severe sequelae though treated in highly intensive care units. Most patients were children under 5 year-old (75% of total), and especially infants between 0 and 2 year-old were found to be at high risk. C
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onvulsion and subsequent unconsciousness were the primary manifestation of encephalopathy, and these CNS symptoms occurred suddenly in a few hours or up to 24 hours after the abrupt onset of high fever. A couple of hours before onset of convulsion, most children who were in age of being able to express their feelings in language, manifested visual and emotional changes, which should be estimated to be the results of limbic system stimulation. Marked deterioration of laboratory findings was noticed; decreased number of platelets and hemoglobin and increased AST/LDH. Glucose levels were normal or high and serum ammonium levels were not increased or within normal range. Examination of CSF was uneventful, all cell counts, glucose, and protein were at normal levels. However, CSF levels of proinflammatory cytokines including IL6 and TNFα were markedly increased. It suggested that in CNS influenza-related factor(s) vigorously stimulates glial cells microglia and astrocytes, thereby accumulating proinflammatory cytokines in CNS and affecting neurons and blood-brain barrier. Laboratory findings in influenza-associated encephalopathy seem to be similar to those seen in septic shock or hemophagocytic syndrome.
The following numbers of patients were enrolled with influenza-associated encephalopathy; 202 patients in 1998/99 season 96 patients in 1999/2000 season, and 56 patients in 2000/2001 season. The first and second surveillance demonstrated that 33% of patients in each season were dead, and 11 to 13% had severe sequelae though treated in highly intensive care units. Most patients were children under 5 year-old (75% of total), and especially infants between 0 and 2 year-old were found to be at high risk. Convulsion and subsequent unconsciousness were the primary manifestation of encephalopathy, and these CNS symptoms occurred suddenly in a few hours or up to 24 hours after the abrupt onset of high fever. A couple of hours before onset of convulsion, most children who were in age of being able to express their feelings in language, manifested visual and emotional changes, which should be estimated to be the results of limbic system stimulation. Marked deterioration of laboratory findings was noticed; decreased number of platelets and hemoglobin and increased AST/LDH. Glucose levels were normal or high and serum ammonium levels were not increased or within normal range. Examination of CSF was uneventful, all cell counts, glucose, and protein were at normal levels. However, CSF levels of proinflammatory cytokines including IL6 and TNFα were markedly increased. It suggested that in CNS influenza-related factor(s) vigorously stimulates glial cells microglia and astrocytes, thereby accumulating proinflammatory cytokines in CNS and affecting neurons and blood-brain barrier. Laboratory findings in influenza-associated encephalopathy seem to be similar to those seen in septic shock or hemophagocytic syndrome.
Infants and children subjected to the surveillance study were not given influenza vaccine with very few exceptions. The Government recommended influenza vaccination, and not to use NSAIDs(diclophenac and mefenamic acid) as anti-febrile because of possible relationship between poor prognosis and usage of NSAIDs.
After publication of "Guideline for Therapy of Influenza-associated Encephalopathy" including hypothermia therapy, plasma exchange, and methylprednisolone-pulses, the third surveillance study was performed in 2000/2001 season. The mortality rate was reduced to 11% and the number of patients with severe sequelae was also decreased to 8% of total patients. Less
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